ARDS disrupts cardiac macrophage subsets

Jana Grune (Berlin)1, G. Bajpai (Boston)2, P. T. Ocak (Boston)2, E. Kaufmann (Montreal)3, N. Kumowski (Boston)2, S. Pabel (Regensburg)4, D. Rohde (Würzburg)5, M. Divangahi (Montreal)3, M. Hulsmans (Boston)2, M. Nahrendorf (Boston)2

1Charité - Universitätsmedizin Berlin CC2: Institut für Physiologie, CCO Berlin, Deutschland; 2Center for Systems Biology Boston, USA; 3Meakins-Christie Laboratories Department of Medicine, Department of Microbiology and Immunology, Department of Pathology Montreal, Kanada; 4Universitätsklinikum Regensburg Klinik und Poliklinik für Innere Med. II, Kardiologie Regensburg, Deutschland; 5Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik I Würzburg, Deutschland


Background: Viral infections can cause acute respiratory distress syndrome (ARDS), systemic inflammation and secondary cardiovascular complications. Lung macrophage subsets change during ARDS, but the role of heart macrophages in cardiac injury during viral ARDS remains unknown. Here we investigate how immune signals typical for viral ARDS affect cardiac macrophage subsets, cardiovascular health and systemic inflammation.

Methods: We assessed cardiac macrophage subsets using immunofluorescence histology of autopsy specimens from 21 Covid-19 patients with SARS-CoV-2-associated ARDS and 33 patients who died from other causes. In mice, we compared cardiac immune cell dynamics after SARS-CoV-2 infection with induced ARDS via intra-tracheal instillation of Toll-like receptor ligands and an ACE2 inhibitor.

Results: In humans, SARS-CoV-2 increased total cardiac macrophage counts and led to a higher proportion of CCR2+ macrophages. In mice, SARS-CoV-2 and virus-free lung injury triggered profound remodeling of cardiac resident macrophages, recapitulating the clinical expansion of CCR2+ macrophages. Treating mice exposed to virus-like ARDS with a TNF-neutralizing antibody reduced cardiac neutrophils, monocytes and CCR2+ MHCIIlo macrophages while also preserving cardiac function. Virus-like ARDS elevated mortality in mice with pre-existing heart failure.

Conclusions: Our data suggest that viral ARDS promotes cardiac inflammation by expanding the CCR2+ macrophage subset and that the associated cardiac phenotypes in mice can be elicited by activating the host immune system even without viral presence in the heart.

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